1. Field of the Invention
This invention relates to monitoring glucose levels, and more particularly relates to an implantable glucose sensor and a method for using same for detection or quantitation of an elevated glucose level in a body fluid.
2. Background Description
Over five million Americans have diagnosed diabetes and another five million are estimated to have undiagnosed diabetes. Diabetes is a chronic metabolic disorder manifested by degenerative disease of the blood vessels, kidneys, retina and nervous system and is characterized by the body's abnormal metabolism of carbohydrates, proteins and fats. Carbohydrates are normally digested to glucose in the gut, the glucose being absorbed into the circulatory system and carried to most cells of the body where, it is utilized as the principal source of nutrition. In one form .of diabetes, the glucose cannot enter the liver, muscle and fat cells in normal amounts for storage or energy use and as a consequence builds up in the blood and urine. Abnormally high blood glucose levels may lead to the accumulation of toxic ketone metabolites often leading to coma and death.
Glucose is normally present in the blood stream at a level of about 0.8 to 1.0 mg/ml and is maintained within this narrow range by a continuous moment to moment sensing and correction of the glucose concentration by hormones released from the pancreas. If glucose concentration in the blood stream rises above the normal range, insulin is released and causes metabolism of glucose which lowers the concentration. If the glucose concentration falls below the normal range, glucogen is released to raise it to normal. The pathological condition of diabetes is primarily due to a long term hyperglycemia resulting from reduced insulin production or release.
Many diabetics control their disease merely by diet and weight control. Others require drug treatment, generally insulin or an oral hypoglycemic agent, to control blood glucose levels. Oral administration of insulin is not practical because it is destroyed by proteolytic enzymes in the gastro-intestinal tract. Injected insulin provides only partial control of the degenerative effects of diabetes, apparently because periodic injections do not closely correspond to changing metabolic requirements consequent to fluctuating blood glucose levels. For this reason, a variety of methods have been proposed for rapid and accurate assessment of blood glucose levels.
Glucose measurement systems known in the art are generally based on the oxidation of glucose by oxygen in the presence of glucose oxidase. U.S. Pat. Nos. 4,452,887 to Kitajina et al., and 4,390,621 and 4,460,684 to Bauer exemplify a chromogenic system in which hydrogen peroxide formed during the oxidation oxidizes a substrate in the presence of peroxidase to produce a color which is measured.
Conversion of the chemical energy of the oxidation reaction to electrical energy, which is measured at electrodes, is the subject of U.S. Pat. Nos. 4,392,933 to Nakamura et al., 4,436,094 to Cerami, 4,431,004 to Bessman et al. and 4,317,817 to Busby.
Cerami, in U.S. Pat. No. 4,330,299, discloses an indicator element, such as a dye, as part of a complex containing a carbohydrate or a lectin. The indicator remains undetected until released from the complex by glucose in direct proportion to the glucose concentration.
Boehringer Mannheim Diagnostics (Indianapolis, IN) recently marketed an in vitro enzyme-based blood glucose monitoring system, (Accu-Chek.TM. Chemstrip bG.TM.), which may be read colorimetrically or photo-electronically.
Fiber optic probes for determination of oxygen pressure in a body fluid have been described. Peterson et al., in U.S. Pat. No. 4,476,870, disclose an implantable device for measurement of partial oxygen pressure in a blood stream based on oxygen quenching of fluorescence.
U.S. Pat. No. 4,399,099 to Buckles discloses a dual fiber optic device useful in a method for measuring glucose concentration. Oxygen permeable sheaths containing an oxygen quenchable fluorescent dye surround optical fibers, one of the sheaths containing glucose oxidase. The enzyme oxidizes glucose and thereby lowers oxygen concentration which is detected by reduced quenching of the fluorescence emission from the dye.
Prior art methods and devices disclosed to date for glucose measurement all suffer from deficiencies such as insufficient accuracy, speed or use of methodology or equipment which is impractical for an implantable device. There remains a definite need for a simple and accurate method for glucose monitoring using a small, light and compact apparatus. It is toward fulfillment of this need that the present invention is directed.